The tools for dissecting the contribution of specific cells to physiological functions and particular behavior have evolved over recent years. Initial studies used electrical and chemical lesions to ablate both neurons and fibers in defined regions. Later investigations made use of direct stimulation through implanted electrodes, however, these studies were hampered by variable activation, the need for permanent implants, and tissue damage. As an alternative to these approaches, recent techniques make use of drug inducible systems to alter gene expression or ion channels to modulate cell activity (Lerchner et al., Neuron 54:35-49). By allowing the selective passage of cations or anions, families of ion channels regulate intracellular ion concentrations, which in turn modulate intracellular functions according to the cell type. The use of ion channels has many advantages; their structure and function are relatively well described; they have a rapid time course of activation, and a broad range of channels exist in mammalian and non-mammalian cells, which may be exploited in the search for the optimum means of modifying cellular activity. This approach was first validated by transgenic expression of a drug-gated channel to modify behavior, however, the time course of effects was relatively slow (hours to days) due to irreversible effects of the ligand. Recently, the non-mammalian channelrhodopsin (ChR2) gene, a light activated cation, has been employed to rapidly activate molecularly defined neurons when exposed to blue light (Boyden E S et al. 2005 Nat Neurosci 8: 1263-1268). This system gives anatomical specificity and temporal control but also has limitations. For example, there are only two variants for activation, thereby limiting the potential for combinatorial activation, and more importantly, activation in vivo requires fiber optic light delivery via implanted devices that are invasive and can interfere with behavior.
The present invention provides methods and compositions for the remote control of cell function based on the use of radiofrequency waves to excite nanoparticles targeted to specific cell types. The invention, uses Nanoparticle Induced Circuit Excitation (NICE) to, for example, regulate ion channels as a means for stimulating the activity of specific cells remotely and non-invasively.